Chemistry:Epacadostat
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| Formula | C11H13BrFN7O4S |
| Molar mass | 438.23 g·mol−1 |
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Epacadostat (previously INCB24360) is an investigational drug for cancer.[1] Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).[1][2][3] Epacadostat inhibits IDO1 by competitively blocking it, without interfering with IDO2 or tryptophan 2,3-dioxygenase (TDO). It has antitumor activity in some models, though is most effective when combined with other immunotherapy agents.[4]
History and clinical trials
As of 2017, the combination of epacadostat with pembrolizumab (Keytruda) was being investigated by Incyte and Merck & Co. in several cancers, as was the combination of epacadostat with nivolumab (Opdivo) by Incyte and Bristol Myers Squibb.[5]
In April 2018, Incyte announced they were halting the Phase III ECHO-301/KEYNOTE-252 (NCT02752074) trial of epacadostat with pembrolizumab for melanoma as the combination therapy missed the first primary endpoint of improving progression-free survival vs. pembrolizumab alone.[6][7] The second primary endpoint of overall survival is not yet determined.[6]
References
- ↑ 1.0 1.1 "Epacadostat". NCI Drug Dictionary. National Cancer Institute. 2011-02-02. https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=685310.
- ↑ "The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy". European Journal of Cancer 76: 167–182. May 2017. doi:10.1016/j.ejca.2017.01.011. PMID 28324751.
- ↑ "INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology". ACS Medicinal Chemistry Letters 8 (5): 486–491. May 2017. doi:10.1021/acsmedchemlett.6b00391. PMID 28523098.
- ↑ "Is There a Clinical Future for IDO1 Inhibitors After the Failure of Epacadostat in Melanoma?". Annual Review of Cancer Biology 4: 241–256. 2020. doi:10.1146/annurev-cancerbio-030419-033635.
- ↑ "Racing in lung cancer again (or still), Merck and BMS expand Incyte combo trials". FiercePharma. 3 April 2017. http://www.fiercepharma.com/marketing/racing-lung-cancer-again-or-still-merck-and-bms-expand-incyte-combo-trials.
- ↑ 6.0 6.1 "Incyte, Merck & Co. Halt Phase III Trial After Epacadostat/Keytruda Combination Fails in Melanoma". 6 April 2018. https://www.genengnews.com/gen-news-highlights/incyte-merck-co-halt-phase-iii-trial-after-epacadostatkeytruda-combination-fails-in-melanoma/81255672.
- ↑ "Incyte Tumbles After Epacadostat Miss". BioCentury. 6 April 2018. https://www.biocentury.com/bc-extra/clinical-news/2018-04-06/incyte-tumbles-after-epacadostat-miss.
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